A US Food and Drug Administration (FDA) investigation of injection-site necrosis in some people who received the 23-valent pneumococcal vaccine has concluded that the benefits of the vaccine outweigh the risks.
No similar safety signal has been detected for the more recently approved 15-valent and 20-valent pneumococcal conjugate vaccines, explain the investigators, led by Brendan Day, MD, MPH, from the FDA’s Center for Biologics Evaluation and Research, in their report published online in a Research Letter in JAMA Internal Medicine.
Reports of injection-site necrosis emerged after the vaccine (Pneumovax 23, Merck) had been approved by the FDA and was administered to a large, diverse, real-world population.
Rare safety events can emerge after FDA approval, as clinical trials may not be able to detect them in a study-group population.
Therefore, “postmarketing safety surveillance is critical to further characterize the safety profile of licensed vaccines,” the investigators point out.
The FDA and the Centers for Disease Control and Prevention monitor the postmarketing safety of licensed vaccines using the Vaccine Adverse Event Reporting System (VAERS), which relies on people who get the vaccines to report adverse events.
After reports indicated a safety signal in 2020, the researchers conducted a case-series review, calculated the reporting rate, and did a PubMed search for similar reports.
They found that the reporting rate for injection-site necrosis was less than 0.2 cases per 1 million vaccine doses administered. The PubMed search yielded two cases of injection-site necrosis after the vaccine.
The 23-valent vaccine helps protect people from pneumococcus bacterial infection. The manufacturer reports that it is for people at least 50 years of age and for children who are at least 2 years of age with medical conditions that put them at elevated risk for infection.
The US package insert has been updated, in the Post-Marketing Experience section, to include injection-site necrosis.
Of the 104 VAERS reports identified by the researchers, 48 met the case definition. Of those cases, most were for skin necrosis (n = 43), five of which also included fat necrosis. The remaining five cases of necrosis affected fascia (n = 2); fat and fascia (n = 1); fat, fascia, and muscle (n = 1); and muscle (n = 1).
In 23 of the 48 cases (47.9%), the reactions were serious, and included one death (unrelated to vaccination).
Seventeen patients (35.4%) were hospitalized and 26 (54.2%) required surgery, most commonly debridement. Eight patients (16.7%) underwent multiple surgical procedures and three (6.3%) required a skin graft.
For patients with skin necrosis (n = 43), the median age was 67 years, and most patients were female (n = 36). Twelve patients were immunocompromised.
Concomitant vaccinations were reported in 10 patients, five of whom got the shot in the same arm as the 23-valent pneumococcal vaccine. A concurrent diagnosis of cellulitis was reported in 16 patients and an abscess was reported in three patients. There were too few cases of fat, fascia, or muscle necrosis to draw conclusions, the researchers report.
Often, skin necrosis was seen after a progression of symptoms, such as redness, pain, or swelling.
“These reports are consistent with published descriptions of injection-site necrosis, which has been reported as a rare complication for many vaccines and injectable drugs,” the investigators report.
Although the researchers couldn’t conclude from the VAERS reports alone that the vaccine injection caused the necrosis, “the timing and the location of reactions at the injection site suggest a possible causal association with the vaccine,” they explain. However, they add, patient comorbidities and poor injection technique may also be contributors.
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.